Sanitizer composition with probiotic/prebiotic active ingredient

ABSTRACT

A sanitizing composition for restoring skin&#39;s natural balance of bacteria and/or increasing the production and/or activity of antimicrobial peptides is provided. The sanitizing composition includes about 0.005 wt. % to 15.0 wt. % of an active ingredient that is one or more of a probiotic, probiotic derivative, prebiotic, and a prebiotic derivative and at least one compound that delivers a sanitizing effect.

RELATED APPLICATIONS

This application claims priority to and the benefit of U.S. ProvisionalPatent Application Ser. No. 62/425,699, entitled “SANITIZER COMPOSITIONWITH PROBIOTIC/PREBIOTIC ACTIVE INGREDIENT” and filed Nov. 23, 2016, theentire disclosure of which is incorporated herein by reference.

BACKGROUND

The skin is the human body's largest organ, colonized by a diverse rangeof microorganisms, the majority of which are harmless or even beneficialto their host. These microorganisms often provide vital functions thatthe human genome has not yet evolved to perform. In this way, the skinconstantly regulates a balance between host-human and microorganism.Disruptions in this delicate balance, on either side, can result inserious skin disorders or infections.

Pathogens on the skin are known to cause illness and may be easilytransmitted from one person to another. Some pathogens stick strongly toskin. Typically, when pathogens stick to skin, they are more difficultto remove or kill using traditional approaches to skin cleaning anddisinfection such as washing with soap or using a waterless sanitizer.Pathogens that are stuck to skin are more dangerous because they remainon the skin longer. The longer the pathogen is on the skin, the more thechance that they will either cause infections on the person with them orbe shared with other people.

There is an increasing interest in finding alternative ways to controlpathogens without the use of more antimicrobials. Probiotics are beingused to control microbes on skin in new ways that do not require the useof antimicrobials. Probiotics are live or inactivated microorganismsthat, when either present as part of the normal microbiota or whenadministered in adequate amounts, confer a health or cosmetic benefit onthe host. Benefits from probiotics can be from the microbial componentsdirectly or can come from the byproducts of bacterial growth.

It is known that some pathogens and beneficial normal (probiotic) skinmicrobes compete with each other for binding sites on skin. U.S. PatentPublication No. 2008/0261916 (the '916 Publication) describes a mixtureof prebiotic ingredients used for the prevention, alleviation ortreatment of diseases or disorders and that can be administeredtopically or orally. However, the '916 Publication does not decrease theadherence of pathogens on skin or reducing pathogen levels on skin anddoes not help prevent skin infections, skin-to-skin germ transmission,skin-to-inanimate object transmission, human-to-animal-to-humantransmission, or human-to-food-to-human transmission.

Antimicrobial peptides (AMPs) comprise a wide range of natural andsynthetic peptides that are made of oligopeptides containing a varyingnumber of amino acids. AMPs may be produced by a host, or by the skinmicrobiota itself. AMPs are essential components of host defense againstinfections present in all domains of life. AMPs are produced by allcomplex organisms and have diverse and intricate antimicrobialactivities. As a whole, these peptides demonstrate a broad range ofantiviral and antibacterial activities through an array of modes ofaction. AMPs have been found to kill Gram-negative and Gram-positivebacteria, certain viruses, parasites and fungi. Some research suggeststhat they can also enhance the internal immunity of complex organismsagainst a broad range of bacteria and viruses. In addition to the innateimmune system present in all animals, vertebrates evolved an adaptiveimmune system based on specific recognition of antigens. Increasingevidence suggests that AMPs released in response to an invasion ofmicrobial can activate adaptive immunity by attractingantigen-presenting dendritic cells to the invasion site.

Therefore, it would be beneficial to design a new sanitizing compositionthat is safe for topical use, restores the natural balance of bacteriaon the skin, including decreasing the adherence of pathogens on theskin, and can also increase the production and/or activity ofantimicrobial peptides.

SUMMARY

According to some exemplary embodiments, a sanitizing composition forrestoring skin's natural balance of bacteria is provided. The sanitizingcomposition includes about 0.005 wt. % to 15.0 wt. % of an activeingredient that is one or more of a probiotic, a probiotic derivative,and a prebiotic. The sanitizing composition also includes one or moreingredients that deliver a sanitizing effect. Application of thesanitizing composition reduces pathogen binding on the surface of theskin by an amount that is statistically significant compared to anotherwise identical sanitizing composition without the activeingredient.

In some exemplary embodiments, the one or more ingredients that delivera sanitizing effect is an anti-microbial agent that can be one or moreof an alcohol and a quaternary ammonium compound. The alcohol can be oneor more C₁₋₈ alcohols, such as methanol, ethanol, propanol, pentanol,hexanol, and isomers and mixtures thereof. In some exemplaryembodiments, the alcohol is included in an amount above about 70 wt. %,based on the total weight of the sanitizing composition.

In some exemplary embodiments, the active ingredient is a probiotic orprobiotic derived ingredient, which can be selected from a strain of oneor more the following: Lactobacillus, strains and derivatives ofClostridia, strains and derivatives of Bifidobacterium, strains andderivatives of Saccharomyces, strains and derivatives of Lactococcus,strains and derivatives of Pedicoccus, strains and derivatives ofEnterococcus, strains and derivatives of Escherichia, strains andderivatives of Alcaligenes, strains and derivatives of Corynebacterium,strains and derivatives of Bacillus, and strains and derivatives ofPropionibacterium. In some exemplary embodiments, the probiotic orprobiotic derived ingredient is a Bacillus ferment.

In some exemplary embodiments, the sanitizing composition comprises fromabout 0.05 to about 5.0 wt. % or from about 0.1 to about 1.0 wt. % ofthe active ingredient, based on the total weight of the sanitizingcomposition.

In some exemplary embodiments, the sanitizing composition furthercomprises one or more skin conditioning agents.

In some exemplary embodiments, the sanitizing composition contains up toabout 20.0 wt. % of a humectant as the skin conditioning agent, selectedfrom the group consisting of propylene glycol, hexylene glycol,1,4-dihydroxyhexane, 1,2,6-hexanetriol, sorbitol, butylene glycol,caprylyl glycol, propanediols, such as methyl propane diol, dipropyleneglycol, triethylene glycol, glycerin (glycerol), polyethylene glycols,ethoxydiglycol, polyethylene sorbitol, glyceryl caprylate/caprate, andcombinations thereof.

In some exemplary embodiments, the sanitizing composition also containsup to about 20.0 wt. % of one or more plug preventing additives, basedon the total weight of the sanitizing composition.

In some exemplary embodiments, the sanitizing composition also containsup to about 10.0 wt. % of a moisturizing ester, selected from the groupconsisting of selected from the group consisting of cetyl myristate,cetyl myristoleate, and other cetyl esters, diisopropyl sebacate,isopropyl myristate, and combinations thereof.

In some exemplary embodiments, the sanitizing composition furthercomprises a carrier, which can be water.

In another exemplary embodiment, a skin treatment method for reducingpathogen binding on skin is provided. The method includes applying asanitizing composition to a skin surface, wherein the sanitizingcomposition includes about 0.005 wt. % to about 15.0 wt. % of an activeingredient. The active ingredient may be one or more of a probiotic, aprobiotic derivative, or a prebiotic. The sanitizing composition alsoincludes one or more ingredients that deliver a sanitizing effect.Application of the sanitizing composition reduces pathogen binding onskin by a statistically significant amount, as compared to an otherwiseidentical sanitizing composition without the active ingredient.

In other exemplary embodiments, a sanitizing composition for increasingthe production and/or activity of antimicrobial peptides is provided.The sanitizing composition includes about 0.005 wt. % to about 15.0 wt.% of an active ingredient that is one or more of a probiotic, aprobiotic derivative, or prebiotic. The sanitizing composition alsoincludes one or more ingredients that deliver a sanitizing effect.Application of the sanitizing composition increases the productionand/or activity of antimicrobial peptides by an amount that isstatistically significant compared to an otherwise identical sanitizingcomposition without the active ingredient.

In some exemplary embodiments, the sanitizing composition increases theproduction and/or activity of defensins by at least about 44% and theproduction and/or activity of cadherins by at least 75%, both relativeto an otherwise identical sanitizing composition without the activeingredient.

In another exemplary embodiment, a skin treatment sanitizing compositionis provided. The sanitizing composition comprises about 0.005 wt. % to15.0 wt. % of an active ingredient comprising one or more of aprobiotic, a probiotic derivative, and a prebiotic, about 40.0 wt. % toabout 95 wt. % of one or more ingredients that deliver a sanitizingeffect, about 0.01 wt. % to about 10.0 wt. % of one or more skinconditioners, and about 0.01 wt. % to about 5.0 wt. % of a viscositymodifier.

In some exemplary embodiments, a sanitizing composition for restoringskin's natural balance of bacteria is provided. “Restoring skin'snatural balance” means helping to change the ratio of transientpathogens to resident microbes (i.e., restores the “good” bacteria andreduces the amount of transient pathogens) The sanitizing compositioncomprises about 0.005 wt. % to 15.0 wt. % of an active ingredientcomprising one or more of a probiotic, a probiotic derivative, orprebiotic, about 40.0 wt. % to about 95.0 wt. % of one or moreingredients that deliver a sanitizing effect, about 0.01 wt. % to about5.0 wt. % of a foaming agent, and about 0.01 wt. % to about 10.0 wt. %of one or more skin conditioners.

In some exemplary embodiments, a sanitizing composition for reducingskin irritation is provided. The sanitizing composition includes about0.005 wt. % to 15.0 wt. % of an active ingredient that is one or more ofa probiotic, a probiotic derivative, and a prebiotic. The sanitizingcomposition also includes about 40.0 wt. % to 95.0 wt. % of one or moreingredients that deliver a sanitizing effect. Application of thesanitizing composition decreases pro-inflammatory mark production and/oractivity by an amount that is statistically significant compared to anotherwise identical sanitizing composition without the activeingredient.

In some exemplary embodiments, the sanitizing composition decreases theproduction and/or activity of pro-inflammatory markers, such asinterleukins, by at least about 30%, relative to an otherwise identicalsanitizing composition without the active ingredient.

According to some exemplary embodiments, a nasal spray sanitizingcomposition is provided. The nasal spray comprises one or more C₁₋₈alcohols and about 0.005 wt. % to about 15.0 wt. % of an activeingredient that is one or more of a probiotic, a probiotic derivative,and a prebiotic. Application of the nasal spray reduces pathogen bindingin the nose by an amount that is statistically significant compared toan otherwise identical nasal spray without the active ingredient.

In some exemplary embodiments, the nasal spray further comprises one ormore fragrances. In some exemplary embodiments, the active ingredientcomprises a topical probiotic and is essentially free of oralprobiotics.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 illustrates an exemplary graph of the relative Interleukin 8expression in sanitizing compositions containing 1.0 wt. % Bonicel™compared to a control.

FIG. 2 illustrates an exemplary graph of the Involiucrin expression incompositions containing 1.0 wt. % Bonicel™ compared to a control.

FIG. 3 illustrates an exemplary graph of the DSC3 expression incompositions containing 0.1 wt. % Bonicel™ compared to a control.

FIG. 4 illustrates an exemplary graph of the HBD-2 expression incompositions containing 0.1 wt. % Bonicel™ and 1.0 wt. % Bonicel™compared to a control.

FIG. 5 illustrates an exemplary graph of the HBD-2 expression incompositions containing 0.1 wt. % Bonicel™ and 1.0 wt. % Bonicel™ thathave been in contact with ethanol compared to a control.

FIG. 6 illustrates an exemplary graph of the response of Staphylococcusaureus adhesion and invasion potential when treated with a probioticBacillus ferment.

FIG. 7 graphically illustrates the affinity of a 1.0% Bonicel™ sanitizerto kill more transient bacteria than resident bacteria.

DETAILED DESCRIPTION

Unless otherwise defined, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this application pertains. Although other methods andmaterials similar or equivalent to those described herein may be used inthe practice or testing of the exemplary embodiments, exemplary suitablemethods and materials are described below. In case of conflict, thepresent specification including definitions will control. In addition,the materials, methods, and examples are illustrative only and notintended to be limiting of the general inventive concepts.

The terminology as set forth herein is for description of the exemplaryembodiments only and should not be construed as limiting the applicationas a whole. Unless otherwise specified, “a,” “an,” “the,” and “at leastone” are used interchangeably. Furthermore, as used in the descriptionof the application and the appended claims, the singular forms “a,”“an,” and “the” are inclusive of their plural forms, unless contradictedby the context surrounding such.

The term “microorganism” or “microbe” as used herein, refers to a tinyorganism, such as a virus, protozoan, fungus, or bacterium that can onlybe seen under a microscope. The collection of microorganisms that livein an environment makes up a microbiota. For example human skinmicrobiota is all of the microbes on skin or a hospital microbiota wouldinclude all of the microbes in a hospital building. The term microbiomeis used when referring to the entire habitat, including the microbiotaas well as their genomes and the surrounding environment of themicrobiota.

The phrase “statistically significant” means p<0.05 for a testcomposition vs. a control that does not contain the active ingredient.The analysis is completed using 1) a T-test (a statistical examinationof two population means) when only comparing one test article vs. onecontrol); or 2) an analysis of variance (ANOVA) test when comparing twoor more test articles vs. controls.

The general inventive concepts relate to a sanitizing composition thatcontains an active ingredient that includes one or more of a probiotic,a probiotic-derived ingredient, and a prebiotic and/or prebiotic-derivedingredient. Generally, the active ingredient helps to restore skin'snatural balance of bacteria and increase the production and/or activityof antimicrobial peptides. In some exemplary embodiments, the sanitizingcomposition disclosed herein prevents pathogens from adhering to asurface, such as human skin or any inanimate surface. Such adherenceprevention includes not only impeding the binding of a pathogen, butalso promoting detachment of any already bound pathogen, and otherwiselimiting the presence of such pathogens on a surface.

In some exemplary embodiments, the sanitizing composition comprises oneor more probiotics and/or probiotic-derived ingredients (probioticderivatives). In general, the probiotic can be any living or deadmicroorganism that provides a health benefit to the host. The probioticderivative can be any derivative of any type of probiotic. In someexemplary embodiments, the derivative is one or more of an excretionfrom a probiotic and a fragment of a probiotic. The fragment can be anyportion of the probiotic microorganism including any portion of its DNAthereof.

Some non-limiting examples of probiotic and probiotic-derivedingredients include strains and derivates of the following families:Actinomycetaceae, Corynebacteriaceae, Nocardiaceae, Intrasporangiaceae,Micrococcaceae, Propionibacteriacea, Bacteroidaceae, Porphyromonadaceae,Flavobacteriaceae, Sphingobacteriaceae, Bacillaceae, Exiguobacteraceae,Gemellaceae, Planococcaceae, Staphlococcaceae, Carnobacteriaceae,Aeorcoccaceae, Lactobacillaceae, Acidaminacoccaceae, Clostridiaceae,Lachnospiraceae, Peptostreptococcaceae, Veillonellaceae,Caulobactereaceae, Acetobacteraceae, Rhodobacteriaceae,Bradyrhizobiaceae, Brucellaceae, Sphingomonadaceae, Comamonadaceae,Neisseriaceae, Enterobaceriaceae, Pseudomonodaceae, Moraxellaceae,Pasteurellaceae, Xanthomonadaceae, Fusobacteriaceae, Chloroflexi,Chloroplasts, Cyanobacteria, and Streptophyta, for example. In someexemplary embodiments, the active ingredient is a probiotic or probioticderived ingredient, which can be selected from a strain of one or morethe following: Lactobacillus, strains and derivatives of Clostridia,strains and derivatives of Bifidobacterium, strains and derivatives ofSaccharomyces, strains and derivatives of Lactococcus, strains andderivatives of Pedicoccus, strains and derivatives of Enterococcus,strains and derivatives of Escherichia, strains and derivatives ofAlcaligenes, strains and derivatives of Corynebacterium, strains andderivatives of Bacillus, and strains and derivatives ofPropionibacterium.

In some exemplary embodiments, the probiotic or probiotic derivedingredient is a ferment of Bacillus coagulans. Bacillus is a genus ofGram-positive, rod-shaped bacteria of the phylum Fimicutes. Bacillus canbe either aerobic or, under certain conditions, anaerobic and producesendospores. Bacillus exhibits a wide range of physiologic propertiesthat allows it to thrive in a number of different habitats—most Bacillusstrains are resistant to heat, cold, radiation, and disinfectants. ABacillus ferment is sold under the trade name Bonicel™ by GanedenBiotech, Inc. in Cleveland, Ohio and is the supernatant produced byBacillus coagulans GBI-30, 6086 (collectively referred to herein as“Bonicel™”). Bonicel™ is produced though a fermentation process whichensures the formulation includes the maximum amounts of enzymes,bateriocins, and L+ Lactic acid. Additional probiotic or probioticderived ingredients may include Repair Complex CLR™, EcoSkin® fromSolabia Group, Leucidal® Liquid SF from Active Micro Technologies,ProSynergen™ from Lonza Group, ProBioBalance CLR™ from CLR, Yogurtene®Balance from Lonza Group, Biodynes™ from Lonza Group, andBifidobacterium Longum Lysate.

In some exemplary embodiments, the active ingredient is one or moreprebiotics and/or prebiotic derived ingredients (prebiotic derivatives).Generally, the prebiotic can be any compound that affects the ecologyand/or environment of the microbiome by increasing good bacteria and/ordecreasing bad bacteria. Non-limiting examples of ways that theprebiotic can affect the ecology and/or environment of the microbiomeinclude, for example, feeding particular organisms, by altering oxygenlevels, by changing temperature, by altering water content, by changingsalinity, and/or by altering nutrient levels/types. Some non-limitingexamples of prebiotic ingredients include alpha and beta-glucanoligosaccharides, trans-galactooligosaccharides, xylooligosaccharide,frutooligosaccharides, lactulose, ginseng, black current extract,sugar-beet extract, garlic extract, bark extract, chicory extract, cornextract, nerolidol extract, xylitol, and pectin. Additional prebioticingredients may include EmulGold™ Fibre by Kerry Ingredients, Genu®Explorer Pectin by CP Kelco, Orafti® from Beneo, VitaFiber™ fromBioNeutra, Konjac Glucomannan Hydrolysates, and Oat Beta Glucan fromVegeTech.

In some exemplary embodiments, the sanitizing composition comprises amixture of probiotics/probiotic derivatives and prebiotics/prebioticderivatives as the active ingredient.

In some embodiments, the active ingredient functions to simulate theproduction and/or activity of antimicrobial peptides and therebyincrease the overall concentration of AMPs on the surface of the skin.In some exemplary embodiments, the sanitizing composition disclosedherein includes an effective amount of active ingredient to increase theproduction and/or activity of at least one antimicrobial peptide on, forexample, the skin. The sanitizing composition can increase theproduction and/or activity of a wide variety of antimicrobial peptides,such as, for example defensins and cathelicidin-related AMPs anddecrease pro-inflammatory factors. Such increased production and/oractivity helps the skin's ability to defend against germs and helpsimprove the skin's innate immunity. While sanitizing compositions thatcan increase the skin's innate immunity or the production and/oractivity on the skin are often discussed herein, it is to be appreciatedthat the sanitizing compositions can provide the same benefits to nails,epithelial cells, as well as other parts of mammalian bodies.

The skin naturally produces AMPs, but the levels produced are notsufficient to produce the desired effect of long lasting germ defenseand innate immunity on the skin. The active ingredient of the exemplaryembodiments described herein has been found to help increase theproduction and/or activity of AMPs at levels significantly higher thanthe skin alone.

In one exemplary embodiment, the sanitizing composition increases theproduction and/or activity of defensins. Defensins are cationic proteinsthat function as host defense peptides and have been found invertebrates, invertebrates, and some plants. Defensins include at leastα-defensins, β-defensins, and θ-defensins. In some exemplaryembodiments, the sanitizing composition increases the production and/oractivity of β-defensins, such as HBD-2.

In some exemplary embodiments, the sanitizing composition increases theproduction and/or activity of cathelicidin-related antimicrobialpeptides. Cathelicidins play a vital role in mammalian innate immunityagainst invasive bacterial infections. In some exemplary embodiments,the sanitizing composition increases the production and/or activity ofthe cathelcidin-related AMP, LL-37.

In other exemplary embodiments, the sanitizing composition decreases theproduction and/or activity of pro-inflammatory factors. One suchpro-inflammatory factor is cytokines, which are a group of smallproteins that are involved in cell signaling. There are numerous groupsof cytokines including chemokiens, interferons, interleukins,lymphokines, and tumor necrosis factors. Interleukins are one group ofcytokines and include 17 different families, interleukins 1-17. In someexemplary embodiments, the sanitizing composition increases theproduction and/or activity of the pro-inflammatory factor, cytokines. Insome exemplary embodiments, the sanitizing composition increases theproduction and/or activity of the cytokine, interleukins, such asinterleukin-8 (IL-8).

In some exemplary embodiments, the sanitizing composition increases theproduction and/or activity of cadherins. In some exemplary embodiments,the cadherins can be within the desmosomal class and within thedesmocollin subclass of cadherins. Cadherins are type-1 trasmembraneproteins that are involved in cell adhesion, specifically adhesionsjunctions in binding cells one another. In this way, they are referredto herein as skin junction biomarkers. In some exemplary embodiments,the sanitizing composition increases the production and/or activity ofthe skin junction biomarker, desmosomals, such as desmocollin-3 (DCS3).

Traditionally, it has been found that compositions used to stimulate theproduction and/or activity of AMPs also cause skin inflammation and/orskin irritation. However, it has been discovered that a sanitizingcomposition comprising the subject active ingredient is capable ofincreasing the production and/or activity of at least one AMP on theskin without causing irritation/inflammation of the skin.

In some embodiments, the active ingredient helps to restore themicrobial balance of bacteria on the skin. A human's skin microbiotaincludes resident skin microorganisms that are continuously present onthe skin. The resident skin microorganisms are usually non-pathogenicand either commensals (not harmful to their host) or mutualistic (offera benefit). Resident skin microorganisms are adapted to survive on skinand they eat, reproduce, and excrete, which has an effect on the skin.However, certain transient skin microorganisms may attempt to colonizethe skin, which could upset a healthy microbiome. Such transient skinmicroorganisms may include pathogens, such as pathogenic bacteria,yeasts, viruses, and molds. The particular make-up of a human'smicrobiome may be different than the make-up of another human's. Aresident skin microorganism on one person may be a transient on another.

While the skin naturally works to regulate the microbiota on thesurface, the active ingredients disclosed herein have been found to helpin regulating and restoring this natural balance.

In some exemplary embodiments, the sanitizing composition comprises upto about 15.0 weight percent (wt. %) of the active ingredient, or up toabout 8.0 wt. %, or up to about 5.0 wt. %, or up to about 3.0 wt. %, orup to about 2.0 wt. % of the active ingredient, based on the totalweight of the sanitizing composition. The sanitizing composition maycomprise at least about 0.001 wt. % of the active ingredient, or atleast about 0.005 wt. %, or at least about 0.01 wt. %, or at least about0.05 wt. %, or at least about 0.1 wt. %, or at least about 0.5 wt. %, orat least about 1.0 wt. % of the active ingredient, based on the totalweight of the sanitizing composition.

In some exemplary embodiments, the effective amount of active ingredientcomprises from about 0.005 to about 15.0 wt. %, or from about 0.02 toabout 5.0 wt. %, or from about 0.5 to about 2.0 wt. %, based on thetotal weight of the sanitizing composition. In other exemplaryembodiments, the effective amount of active ingredient comprises about0.1 to about 1.0 wt. %, based on the total weight of the sanitizingcomposition. In one exemplary embodiment, the sanitizing compositioncomprises about 0.08 to about 0.2 wt. % of the active ingredient, basedon the total weight of the sanitizing composition.

In some exemplary embodiments, the sanitizing composition is asanitizing composition used for application to surfaces, such as thehuman skin. In some other exemplary embodiments, the sanitizingcomposition is used for application in various human orifices, such asthe nose. While surfaces on the human body, such as the skin or nose arediscussed herein, it is to be appreciated that the compositions andmethods disclosed herein can be used on non-mammalian and inanimateobjects and surfaces.

The sanitizing composition may be in the form of a gel, a foam, a salve,a wipe, a cream, etc. A wide variety of vehicles may be used to deliverthe sanitizing composition, such as, for example pads, bandages,patches, sticks, aerosol dispersers, pump sprays, trigger sprays,canisters, foam pumps, wipes, and the like. The sanitizing compositionmay be applied to the skin before, during, or after skin cleaning. Insome exemplary embodiments, the sanitizing composition is applied afterskin cleaning.

In some exemplary embodiments, the sanitizing composition comprises oneor more ingredients that have a sanitizing effect. The term “ingredientwith a sanitizing effect” is meant to include any compound, ingredient,molecule, or combination or blend thereof that achieves at least a 2-logreduction in the number of viable microorganisms in vitro after 60seconds according to the ASTM E2783 11(2016) time kill test method. Theingredient with a sanitizing effect can be an anti-microbial agent.Anti-microbial agents are compounds that kill and/or protect against thegrowth of microorganisms.

In some exemplary embodiments, the ingredient with a sanitizing effectis one or more of alcohol, povidone-iodine, triclosan, triclocarban,chlorohexidine, chlorine, hexachlorophene, iodine, chloroxyenol,chlorine dioxide, oxidizing agents, polyhexamethylene biguanide (PHMB),hydrogen peroxide, phenoxyethanol, iodine, antimicrobial peptides,hypochlorites, lysozymes, alkyl gallates, quinones, catechins, urea,biguanide, oxygen, and quaternary ammonium compounds such asbenzalkonium chloride or benzethonium chloride. In some exemplaryembodiments, the ingredient with a sanitizing effect is an aldehydedonor, such as a formaldehyde donor. In some exemplary embodiments theingredient with a sanitzing effect is a surfactant. In some exemplaryembodiments, the surfactant is an anionic surfactant, a cationicsurfactant, or a nonionic surfactant.

In some exemplary embodiments, the ingredient with a sanitizing effectis an acid. In some exemplary embodiments, the acid is an organic acid.In some exemplary embodiments, the acid is one or more of citric acid,lactic acid, hypochlorous acid, caffeic acid, and the like. In someexemplary embodiments, the acid is a peracid, such as peracitic acid,perlactic acid, peroctanoic acid, perbenzoic acid, peracetic acid,perpropionic acid, performic acid, and the like. The peracid can be aninorganic or organic peracid. In some exemplary embodiments, theingredient with a sanitizing effect is an essential oil and/orderivative thereof. Non-limiting examples of such compounds includecarvacrol, thymol, linalool, farnesol, and the like. In some exemplaryembodiments, the ingredient with a sanitizing effect is a carboxylicacid, such as a mono-, di-, tri-, or tetra-carboxylic acid or apolymeric carboxylic acid.

In some exemplary embodiments, the ingredient with a sanitizing effectis a compound that contains one or more of silver and copper or alloysthereof (such as brasses, bronzes, cupronickel, and the like). In someexemplary embodiments, the silver or copper has been ionized. In someexemplary embodiments, the ingredient with a sanitizing effect iselemental copper or elemental silver. In some exemplary embodiments, theingredient with a sanitizing effect is a silver salt or copper salt. Insome other exemplary embodiments, the ingredient with a sanitizingeffect is a titanium dioxide based solution.

In some exemplary embodiments, the ingredient with a sanitizing effectis an organic peroxide, a phenolic compound, a free radical, or aglycol. In some exemplary embodiments, the ingredient with a sanitizingeffect is an ion, such as a hydroxyl ion or a metal ion. In someexemplary embodiments, the ingredient with a sanitizing effect is anycompound that has been identified or approved by the United States Foodand Drug Administration as being suitable as an activeingredient/anti-microbial agent in a sanitizing composition.

In some exemplary embodiments, the ingredient that has a sanitizingeffect in the sanitizing composition is an alcohol or combination ofalcohols. By alcohol, it is meant any organic compound which has ahydroxyl functional group bonded to a saturated carbon atom. Alcohol hasantimicrobial properties and has the ability to kill many forms ofbacteria, fungi, and viruses. In some embodiments, the alcohol is a C₁₋₈alcohol, i.e. an alcohol containing 1 to 8 carbon atoms. Such alcoholsmay be referred to as lower alkanols. Examples of lower alkanolsinclude, but are not limited to, methanol, ethanol, propanol, butanol,pentanol, hexanol, and isomers and mixtures thereof. The alcohol may beeither pure alcohol or denatured alcohol. In one or more exemplaryembodiments, the alcohol comprises ethanol, propanol, or butanol, orisomers or mixtures thereof. In one or more exemplary embodiments, thealcohol comprises isopropanol. In other exemplary embodiments, thealcohol comprises ethanol. In one or more exemplary embodiments, thesanitizing composition comprises a mixture of alcohols. In one or moreexemplary embodiments, the sanitizing composition comprises a mixture ofethanol and isopropanol. In one or more exemplary embodiments, thesanitizing composition comprises a mixture of isopropanol andn-propanol. In one exemplary embodiment, the sanitizing compositioncomprises ethanol.

While C₁₋₈ alcohols are discussed herein as able to deliver thenecessary sanitizing effect, it is envisioned that longer alcohols(alcohols with more than 8 carbon atoms), or alcohols with various otherfunctional groups would be similarly suitable. For example, in additionto the hydroxyl functional group, the alcohol may further containesters, carboxylic acids, ethers, amides, amines, alkyl halides,phenyls, as well as other carbonyl-containing functional groups. Thealcohol can also be an aliphatic alcohol or an aromatic alcohol.

In some exemplary embodiments, the sanitizing composition comprises atleast about 1.0 wt. % C₁₋₈ alcohol, based on the total weight of thesanitizing composition. In one embodiment, the sanitizing compositioncomprises at least about 2.0 wt. % C₁₋₈ alcohol, in another embodiment,the sanitizing composition comprises at least about 10.0 wt. % C₁₋₈alcohol, in another embodiment, the sanitizing composition comprises atleast about 20.0 wt. % C₁₋₈ alcohol, in another embodiment, thesanitizing composition comprises at least about 40.0 wt. % C₁₋₈ alcohol,in another embodiment, the sanitizing composition comprises at leastabout 50.0 wt. % C₁₋₈ alcohol, in another embodiment, the sanitizingcomposition comprises at least about 60.0 wt. % C₁₋₈ alcohol, in anotherembodiment, the sanitizing composition comprises at least about 65.0 wt.% C₁₋₈ alcohol, in yet another embodiment, the sanitizing compositioncomprises at least about 70.0 wt. % C₁₋₈ alcohol, and in still yetanother embodiment, the sanitizing composition comprises at least about80.0 wt. % C₁₋₈ alcohol, based on the total weight of the sanitizingcomposition. In other embodiments, the sanitizing composition comprisesfrom about 60.0 to about 95.0 wt. % C₁₋₈ alcohol, based on the totalweight of the sanitizing composition. In other exemplary embodiments,the sanitizing composition comprises from about 73.0 to about 78.0 wt. %C₁₋₈ alcohol, based on the total weight of the sanitizing composition.More or less alcohol may be required in certain instances, dependingparticularly on other ingredients and/or the amounts thereof employed inthe sanitizing composition.

The ability to use the active ingredients of the exemplary embodimentsdescribed herein in the presence of alcohol was particularly surprising.Typically, the presence of alcohol is thought to kill or disruptbacteria (such as Bacillus coagulans in Bonicel™). The exact modethereof is not clear, however the following probable effects have beenoffered: (1) alcohol affects and at high concentrations actuallydisrupts the lipid cell membrane changing mobility therein, (2) alcoholtraverses the cell membrane and denatures proteins, and (3) alcohol actsas a solvent, changing the environment in which enzymes catalyzereactions. However, surprisingly, the present composition including highconcentrations of alcohol and a probiotic, probiotic-derived orprebiotic active ingredient was prepared without observing thesetraditional adverse reactions between the alcohol and bacteria. In fact,in some exemplary embodiments, the prebiotic, probiotic, orprobiotic-derived ingredient has enhanced effectiveness as compared toperformance in non-alcohol systems.

In other exemplary embodiments, where the ingredient with a sanitizingeffect is not alcohol, the amount of the ingredient is not particularlylimited. In some exemplary embodiment, the ingredient with a sanitizingeffect can be added in an amount up to about 95.0 wt. %, or about 85.0wt. %, or about 75.0 wt. %, or about 65.0 wt. %, based on the totalweight of the sanitizing composition. In other exemplary embodiments,the ingredient with a sanitizing effect can be added in an amount as lowas about 0.001 wt. %, or about 0.01 wt. %, or about 0.1 wt. %. In someexemplary embodiments, the ingredient with a sanitizing effect can beadded in an amount from about 0.01 to about 15.0 wt. %, based on thetotal weight of the sanitizing composition. In some exemplaryembodiments, the ingredient with a sanitizing effect is added in anamount from about 0.5 to about 7.5 wt. %, or about 0.75 to about 5.0 wt.%, or from about 1.0 to about 4.0 wt. %, based on the total weight ofthe sanitizing composition.

In some exemplary embodiments, the sanitizing composition comprises acarrier. The carrier can be any suitable compound able to effectivelydeliver and/or transport the sanitizing composition. In some exemplaryembodiments, the carrier is water or a base cleaner. In other exemplaryembodiments, the sanitizing composition does not include any carrier andis delivered as a concentrate.

In some exemplary embodiments, the sanitizing composition includes wateras the carrier in an amount quantum sufficit (q.s.). In some exemplaryembodiments, the sanitizing composition comprises at least about 1.0 wt.% water, in another embodiment the sanitizing composition comprises atleast about 10.0 wt. % water, in another embodiment, the sanitizingcomposition comprises at least about 20.0 wt. % water, in anotherembodiment, the sanitizing composition comprises at least about 30.0 wt.% water, in another embodiment, the sanitizing composition comprises atleast about 40.0 wt. % water, in another embodiment, the sanitizingcomposition comprises at least about 50.0 wt. % water, and in yetanother embodiment, the sanitizing composition comprises at least about60.0 wt. % water, and in still yet another embodiment, the sanitizingcomposition comprises at least about 70.0 wt. % water, based on thetotal weight of the sanitizing composition. In other embodiments, thesanitizing composition comprises from about 20.0 wt. % to about 30.0 wt.% water, based on the total weight of the sanitizing composition. In oneexemplary embodiment, the sanitizing composition comprises from about20.0 to about 24.0 wt. % water, based on the total weight of thesanitizing composition. More or less water may be required in certaininstances, depending particularly on other ingredients and/or theamounts thereof employed in the sanitizing composition.

In one or more exemplary embodiments, the sanitizing compositionincludes one or more skin-conditioners. Various classes or types ofskin-conditioners can be used such as humectants, emollients, and othermiscellaneous compounds which exhibit occlusive properties uponapplication to the skin. Non-limiting examples of suitable skinconditioners and emollients include aloe, vitamin E, vitamin E acetate(tocopheryl acetate), Vitamin B₃ (niacinamide), C₆₋₁₀ alkane diols,sodium salt of pyroglutamic acid (sodium PCA), PEG-7 glyceryl cocoate,coco-glucoside and/or glyceryl oleate (Lamisoft® PO), andpolyquaternium, such as polyquaternium 10 and 39.

In some exemplary embodiments, if an emollient or one of themiscellaneous skin-conditioners is included, such compound can beincluded in the sanitizing composition in an amount from about 0.0001 toabout 10.0 wt. %, in other embodiments, from about 0.0005 to about 5.0wt. %, based on the total weight of the sanitizing composition. In oneexemplary embodiment, the miscellaneous skin conditioner is present inan amount from about 0.1 to about 2.0 wt. %, based on the total weightof the sanitizing composition, and in yet another exemplary embodiment,from about 0.5 to about 1.0 wt. %, based on the total weight of thesanitizing composition.

In some exemplary embodiments, the sanitizing composition includes oneor more humectants as the skin conditioner. Non-limiting examples ofhumectants include propylene glycol, hexylene glycol,1,4-dihydroxyhexane, 1,2,6-hexanetriol, sorbitol, butylene glycol,caprylyl glycol, propanediols, such as methyl propane diol, dipropyleneglycol, triethylene glycol, glycerin (glycerol), polyethylene glycols,ethoxydiglycol, polyethylene sorbitol, and combinations thereof. Otherhumectants include glycolic acid, glycolate salts, lactate salts, urea,hydroxyethyl urea, alpha-hydroxy acids, such as lactic acid, sodiumpyrrolidone carboxylic acid, hyaluronic acid, chitin, glycerylcaprylate/caprate (GCC), and the like. In one exemplary embodiment, thehumectant is a mixture of caprylyl glycol and glycerin.

Examples of polyethylene glycol humectants include PEG-4, PEG-6, PEG-7,PEG-8, PEG-9, PEG-10, PEG-12, PEG-14, PEG-16, PEG-18, PEG-20, PEG-32,PEG-33, PEG-40, PEG-45, PEG-55, PEG-60, PEG-75, PEG-80, PEG-90, PEG-100,PEG-135, PEG-150, PEG-180, PEG-200, PEG-220, PEG-240, and PEG-800.

In some exemplary embodiments, the humectant is included in thesanitizing composition in an amount up to about 20.0 wt. %, or up toabout 15.0 wt. %, or up to about 12.0 wt. %, or up to about 10.0 wt. %,or up to about 8.0 wt. % or up to about 8.0 wt. %, or up to about 3.0wt. %, based on the total weight of the sanitizing composition. In someexemplary embodiments, the humectant is included in an amount from about0.001 wt. %, or from about 0.01 wt. %, or from about 0.05 wt. %, or fromabout 0.1 wt. %, or from about 0.5 wt. %, or from about 0.7 wt. %, orfrom about 1.0 wt. %, or from about 1.5 wt. %, or from about 2.0 wt. %,based on the total weight of the sanitizing composition. In oneexemplary embodiment, the humectant is included in an amount from about0.4 to about 3.0 wt. %, based on the total weight of the sanitizingcomposition. In some exemplary embodiments, the humectant is included inan amount from about 0.005 to about 10.0 wt. %, or from about 0.01 toabout 5.0 wt. %, based on the total weight of the sanitizingcomposition. In one exemplary embodiment the humectant is included in anamount from about 0.1 to about 4.0 wt. %, based on the total weight ofthe sanitizing composition.

In some exemplary embodiments, the sanitizing composition furthercomprises a plug-preventing additive. In general, the additive preventsthe hydroalcoholic gel from coagulating into solid or semi-solidmaterial that may deposit onto a surface or plug a dispenser nozzle. Insome exemplary embodiments, the plug-preventing additive can also, asdiscussed above, act as the humectant.

In one exemplary embodiments, the plug-preventing additive comprises ahydrocarbon chain with two or more carbon atoms. The hydrocarbon can bebranched or straight and can also be cyclic or linear. The hydrocarboncan have any number of various functional groups including, but notlimited to, amines, esters, carboxylic acids, ethers, amides, alkylhalides, alcohols, phenyls, as well as other carbonyl-containingfunctional groups. The hydrocarbon molecule can be anionic, cationic, ornon-ionic.

In one exemplary embodiment, the hydrocarbon contains one or moreesters. In some exemplary embodiments, the plug-preventing additivecomprises a monomeric or polymeric di-ester, tri-ester, tetra-ester,penta-ester, or hexa-ester, or a polymeric monoester. In one or moreembodiments, the plug-preventing additive includes one or more of C₁-C₃₀alcohol esters of C₁-C₃₀ carboxylic acids, ethylene glycol monoesters ofC₁-C₃₀ carboxylic acids, ethylene glycol diesters of C₁-C₃₀ carboxylicacids, propylene glycol monoesters of C₁-C₃₀ carboxylic acids, propyleneglycol diesters of C₁-C₃₀ carboxylic acids, C₁-C₃₀ carboxylic acidmonoesters and polyesters of polypropylene glycols, C₁-C₃₀ carboxylicacid monoesters and polyesters of polypropylene glycols, C₁-C₃₀carboxylic acid monoesters and polyesters of C₄-C₂₀ alkyl ethers, C₁-C₃₀carboxylic acid monoesters and polyesters of di-C₈-C₃₀ alkyl ethers, andmixtures thereof.

Non-limiting examples of plug-preventing additives with esters includeacetyl tributyl citrate, acetyl triethyl citrate, acetyl triethylhexylcitrate, acetyl trihexyl citrate, butyl benzyl phthalate, butyl phthalylbutyl glycolate, butyroyl trihexyl citrate, dibutyl adipate,dibutyloctyl malate, dibutyl oxalate, dibutyl phthalate, dibutylsebacate, dicapryl adipate, dicaprylyl/capryl sebacate, diethyleneglycol dibenzoate, diethylene glycol diethylhexanoate/diisononanoate,diethylene glycol diisononanoate, diethylene glycol rosinate,diethylhexyl adipate, diethylhexyl phthalate, diethylhexyl sebacate,diethylhexyl succinate, diethylhexyl terephthalate, diethyl oxalate,diethyl phthalate, diethyl sebacate, diethyl succinate, diisoamylmalate, diisobutyl adipate, diisobutyl maleate, diisobutyl oxalate,diisocetyl adipate, diisocetyl dodecanedioate, diisodecyl adipate,diisononyl adipate, diisocetyl adipate, diisooctyl maleate, diisooctylsebacate, diisopropyl adipate, diisopropyl oxalate, diisopropylsebacate, diisopropyl dimer dilinoleate, diisostearyl adipate,diisostearyl fumarate, diisostearyl glutarate, diisostearyl malate,diisostearyl sebacate, dimethyl adipate, dimethyl oxalate, dimethylphthalate, dioctyldodecyl adipate, Dioctyldodecyl Dimer Dilinoleate,Dioctyldodecyl Dodecanedioate, Dioctyldodecyl Fluoroheptyl Citrate,Dioctyldodecyl IPDI, Dioctyldodecyl Lauroyl Glutamate, DioctyldodecylMalate, Dioctyldodecyl Sebacate, Dioctyldodecyl Stearoyl Glutamate,dipentaerythrityl hexa C₅₋₉ acid esters, dipentaerythrityl hexa C₅₋₁₀acid esters, dipropyl oxalate, pentaerythrityl tetra C₅₋₉ acid esters,pentaerythrityl tetra C₅₋₁₀ acid esters, tributyl citrate,tricaprylyl/capryl trimellitate, triethyl citrate, triethylene glycoldibenzoate, triethylene glycol rosinate, triethylhexyl citrate,triethylhexyl trimellitate, trimethylpentanediyl dibenzoate, trimethylpentanyl diisobutyrate, polyglyceryl-6 pentacaprylate, polyglyceryl-10pentahydroxystearate, polyglyceryl-10 pentaisostearate, polyglyceryl-10pentalaurate, polyglyceryl-10 pentalinoleate, polyglyceryl-5pentamyristate, polyglyceryl-4 pentaoleate, polyglyceryl-6 pentaoleate,polyglyceryl-10 pentaoleate, polyglyceryl-3 pentaricinoleate,polyglyceryl-6 pentaricinoleate, polyglyceryl-10 pentaricinoleate,polyglyceryl-4 pentastearate, polyglyceryl-6 pentastearate,polyglyceryl-10 pentastearate, sorbeth-20 pentaisostearate, sorbeth-30pentaisostearate, sorbeth-40 pentaisostearate, sorbeth-50pentaisostearate, sorbeth-40 pentaoleate, sucrose pentaerucate, andtriacetin, combinations thereof. In some exemplary embodiments thehydrocarbon plug-preventing additive is selected from one or more ofispropyl myristate and diisopropyl sebacate.

In one or more embodiments, the plug-preventing additive comprises apolymeric ester. The polymeric ester can include one or more estergroups.

In some exemplary embodiments, the polymer chain includes a polyethyleneglycol (PEG) chain, a polypropylene glycol (PPG), or a combinationthereof. In one or more embodiments, the polymer chain includes up toabout 12 PEG units, PPG units, or a combination thereof. In someexemplary embodiments, the polymer chain includes up to about 10 PEGunits, PPG units, or a combination thereof. In some exemplaryembodiments, the polymer chain includes up to about 8 PEG units, PPGunits, or a combination thereof. In some exemplary embodiments, thepolyether polymer chain includes from about 1 to about 12 PPG or PEGunits, or from about 2 to about 8 PPG or PEG units, or a combinationthereof.

Examples of polymeric esters include those that may be represented bythe following formula

wherein R¹ is a linear or branched alkyl group having from 1 to 28carbon atoms, each R², which may be the same or different, includes apolyether chain having up to about 12 PEG or PPG groups, or acombination thereof, and each R³, which may be the same or different,includes an alkyl or alkylene group having from 1 to about 30 carbonatoms, and wherein each R³ group is attached to R² via an ether linkage.

In some exemplary embodiments, R¹ includes up to about 20 carbon atoms,or up to about 10 carbon atoms, or up to about 8 carbon atoms. In someexemplary embodiments, R³ may be represented by the formulaCH₃(CH₂)_(z)O—, wherein z is an integer from 1 to about 21, or from 2 toabout 17, or from 3 to about 15.

In one or more embodiments, the polymeric ester may be represented bythe following formula

wherein R⁴ includes a linear or branched, alkyl or alkylene group havingfrom 1 to about 22 carbon atoms. In some exemplary embodiments, R⁴ maybe represented by the formula CH₃(CH₂)_(z)—, wherein some exemplaryembodiments z is an integer from 1 to about 21, or from 2 to about 17,or from 3 to about 15. In some exemplary embodiments, n is an integerfrom 1 to about 20, or from 2 to about 10. In some exemplary embodimentsx is an integer up to about 12, or up to about 10, or up to about 8, oris zero. In some exemplary embodiments, y is an integer up to about 12,or up to about 10, or up to about 8, or is zero. Examples of polymericesters further include those that may be represented by the followingformula

wherein R¹, R², and R³ are as described hereinabove.

Examples of polymeric esters include any of the above di-, tri, tetra-,penta-, or hexa-esters modified to include a PPG, PEG, or PPG/PEGpolymer chain of the appropriate length. Specific examples includeDi-PPG-3-ceteth-4 adipate, Di-PPG-2-myreth-10 adipate, Di-PPG-3-myristylether adipate, and PPG-2 myristyl ether propionate. In some exemplaryembodiments, a mixture of one or more polymeric esters and one or moremonomeric di-, tri-, tetra-, penta-, or hexa-esters may be employed asplug-preventing additives.

In other exemplary embodiments the plug-preventing comprises one or morediols, that is compounds with two hydroxyl groups. Plug-preventingadditives that contain more or less hydroxyl groups (i.e., one hydroxylgroup and three or more hydroxyl groups) are also within the purview ofthe exemplary embodiments disclosed herein. In one or more exemplaryembodiments the diol is a C₆₋₁₀ alkane diol and/or a straight chainC₆₋₁₀ alkane diol. Non-limiting examples of suitable diols include1,2-hexanediol, 1,2-octanediol (often referred to as caprylyl glycol),1,9-nonanediol, 1,2-decanediol, 1,10-decanediol, or mixtures and blendsthereof. It is envisioned that the diol can contain any other functionalgroups including, for example, esters, carboxylic acids, ethers, amides,amines, alkyl halides, phenyls, as well as other carbonyl-containingfunctional groups. In some exemplary embodiments, the plug-preventingagent contains at least one ester and/or at least one amide group. Insome exemplary embodiments, the plug-preventing agent is selected fromglyceryl caprylate/caprate (GCC) and cocoamide diethanolamine.

If separate from the humectant, the plug-preventing additive may beincluded in the sanitizing composition in an amount up to about 20.0 wt.%, or up to about 15.0 wt. %, or up to about 12.0 wt. %, or up to about10.0 wt. %, or up to about 8.0 wt. % or up to about 5.0 wt. %, or up toabout 3.0 wt. %, based on the total weight of the sanitizingcomposition. In some exemplary embodiments, the plug-preventing agent isincluded in an amount from about 0.001 wt. %, or from about 0.01 wt. %,or from about 0.05 wt. %, or from about 0.1 wt. %, or from about 0.5 wt.%, or from about 0.7 wt. %, or from about 1.0 wt. %, or from about 1.5wt. %, or from about 2.0 wt. %, based on the total weight of thesanitizing composition. In one exemplary embodiment, the plug-preventingadditive is included in an amount from about 0.05 to about 4.0 wt. %, orfrom about 0.1 to about 1.0 wt. %, or from about 0.15 to about 0.7 wt.%, or from about 0.2 to about 0.7 wt. %, based on the total weight ofthe sanitizing composition.

In certain embodiments, the plug-preventing additive is added to thecomposition as a solution or emulsion. That is, the plug-preventingadditive can be premixed with a carrier to form a solution or emulsion,with the proviso that the carrier does not deliriously effect theability of the sanitizing composition to sanitize and kill non-envelopedviruses. Examples of carriers include water, alcohol, glycols such aspropylene or ethylene glycol, ketones, linear and/or cyclichydrocarbons, triglycerides, carbonates, silicones, alkenes, esters suchas acetates, benzoates, fatty esters, glyceryl esters, ethers, amides,polyethylene glycols and PEG/PPG copolymers, inorganic salt solutionssuch as saline, and mixtures thereof. It will be understood that, whenthe plug-preventing additive is premixed to form a plug-preventingadditive solution or emulsion, the amount of solution or emulsion thatis added to the sanitizing composition is selected so that the amount ofplug-preventing additive falls within the ranges set forth hereinabove.

The sanitizing composition may further comprise one or more conditioningor moisturizing esters. Examples of such conditioning or moisturizingesters include cetyl myristate, cetyl myristoleate, and other cetylesters, diisopropyl sebacate, and isopropyl myristate. The ester may bepresent in an amount of up to about 10.0 wt. %, or up to about 8.0 wt.%, or up to about 5.0 wt. %, or up to about 3.0 wt. %, or up to about2.0 wt. %, or up to about 1.0 wt. %, based on the total weight of thesanitizing composition. In some exemplary embodiments, the moisturizingester is present in an amount from about 0.001 wt. %, or from about0.005 wt. %, or from about 0.01 wt. %, or from about 0.05 wt. %, or fromabout 0.1 wt. %, or from about 0.25 wt. %, or from about 0.5 wt. %, orfrom about 1.0 wt. %, based on the total weight of the sanitizingcomposition. In one exemplary embodiment, the moisturizing ester ispresent in an amount between 0.01 to 0.3 wt. %, based on the totalweight of the sanitizing composition. In another exemplary embodiment,the moisturizing ester is present in an amount between 0.05 wt. % and0.25 wt. %, based on the total weight of the sanitizing composition.

In one or more embodiments, the sanitizing composition may include oneor more emulsifying agents. Examples of emulsifying agents includestearyl alcohol, sorbitan oleate trideceth-2, poloxamers, andPEG/PPG-20/6 dimethicone. In some exemplary embodiments, the emulsifyingagent is present in an amount of up to about 10.0 wt. %, based on thetotal weight of the sanitizing composition. In other exemplaryembodiments, the emulsifying agent is present in an amount of from about0.1 to about 5.0 wt. %, or from about 0.5 to about 2.0 wt. %, based onthe total weight of the sanitizing composition.

The sanitizing composition may further comprise one or more depositionenhancers. A suitable deposition enhancer works unidirectionally andwill allow ingredients within the composition to penetrate deeper intothe stratum corneum whilst preventing the loss of materials from theskin. Advantageously, the deposition enhancer provides a cosmeticallyacceptable skin feel to the formulation.

In one or more embodiments, the deposition enhancers include one or moreof surfactants, bile salts and derivatives thereof, chelating agents,and sulphoxides.

Some examples of acceptable deposition enhancers include dimethylsulphoxides (DMSO), DMA, DMF, 1-dodecylazacycloheptan-2-one (azone),pyrrolidones such as 2-Pyrrolidone (2P) and N-Methyl-2-Pyrrolidone(NMP), long-chain fatty acids such as oleic acid and fatty acids with asaturated alkyl chain length of about C₁₀-C₁₂, essential oils, terpenes,terpenoids, oxazolidinones such as 4-decyloxazolidin-2-one, sodiumlauryl sulfate (SLS), sodium laureate, polysorbates, sodium glyacolate,sodium deoxycholate, caprylic acid, EDTA, phospholipids, C₁₂₋₁₅ AlkylBenzoate, pentylene glycol, ethoxydiglycol,polysorbate-polyethylenesorbitan-monolaurate, and lecithin.

In one or more exemplary embodiments, the deposition enhancer is aquaternary ammonium compound such aspolyquaternium-6,-7,-10,-22,-37,-39,-74 or -101.

The deposition enhancer may be included in the sanitizing composition inan amount from about 0.005 wt. % to about 10.0 wt. %, in otherembodiments, from about 0.01 wt. % to about 5.0 wt. %, and in otherembodiments, from about 0.05 wt. % to about 3.0 wt. %, based on thetotal weight of the sanitizing composition.

In one or more exemplary embodiments, the deposition enhancer comprisesa hydroxy-terminated polyurethane compound chosen frompolyolprepolymer-2, polyolprepolymer-14, and polyolprepolymer-15.Polyolprepolymer-2 is sometimes referred to as PPG-12/SMDI copolymer.The polyurethane compound may be present in the sanitizing compositionin an amount from about 0.005 wt. % to about 5.0 wt. %, in otherembodiments, from about 0.01 wt. % to about 3.0 wt. %, and in otherembodiments, from about 0.05 wt. % to about 1.0 wt. %, based on thetotal weight of the sanitizing composition.

The sanitizing composition may further comprise one or moreanti-irritants. Anti-irritants reduce signs of inflammation on the skinsuch as swelling, tenderness, pain, itching, or redness. There are threemain types of anti-irritants, all of which are envisioned as beingapplicable in the exemplary embodiments described herein: (1) compoundsthat operate by complexing the irritant itself, (2) compounds that reactwith the skin to block reactive sites preventing the irritant fromreacting directly with the skin, and (3) compounds that prevent physicalcontact between the skin and irritant.

Some exemplary examples of suitable anti-irritants include Aloe Vera,allantoin, anion-cation complexes, aryloxypropionates, azulene,carboxymethyl cellulose, cetyl alcohol, diethyl phthalate, Emcol E607,ethanolamine, glycogen, lanolin, N-(2-Hydroxylthyl) Palmitamide,N-Lauroyl Sarcosinates, Maypon 4C, mineral oils, miranols, Myristyllactate, polypropylene glycol, polyvinyl pyrrolidone (PVP), tertiaryamine oxides, thiodioglycolic acid, and zirconia. In one exemplaryembodiment, the anti-irritant is avenanthrmides (Avena Sativa (oat),kernel oil, and glycerin) and niacinamide.

The anti-irritant may be included in the sanitizing composition in anamount up to about 10.0 wt. %, in other embodiments, from about 0.005wt. % to about 3.0 wt. %, and in other embodiments, from about 0.01 wt.% to about 1.0 wt. %, based on the total weight of the sanitizingcomposition.

The sanitizing composition may further comprise a fragrance. Any scentmay be used in the sanitizing composition including, but not limited to,any scent classification on a standard fragrance chart, such as floral,oriental, woody, and fresh. Exemplary scents include cinnamon, clove,lavender, peppermint, rosemary, thyme, thieves, lemon, citrus, coconut,apricot, plum, watermelon, ginger and combinations thereof.

The fragrance can be included in the sanitizing composition in an amountfrom about 0.005 wt. % to about 5.0 wt. %, in other embodiments, fromabout 0.01 wt. % to about 3.0 wt. %, and in other embodiments, fromabout 0.05 wt. % to about 1.0 wt. %, based on the total weight of thesanitizing composition. The fragrance can be any made of any perfume,essential oil, aroma compounds, fixatives, terpenes, solvents, and thelike. In some exemplary embodiments, the essential oils may include, forexample, one or more of Limonene, Citrus Aurantium Dulcis (Orange) PeelOil, Eucalyptus Globulus Leaf Oil, Citrus Grandis (Grapefruit) Peel Oil,Linalool, Litsea Cubeba Fruit Oil, Lavandula Hybrida Oil, Abies SibiricaOil, Mentha Citrata Leaf Extract, Coriandrum Sativum (Coriander) FruitOil, Piper Nigrum (Pepper) Fruit Oil, and Canarium Luzonicum GumNonvolatiles.

The sanitizing composition may further comprise a wide range of optionalingredients that do not deleteriously affect the composition's abilityto stimulate AMP production and/or activity and that do notdeleteriously affect the composition's ability to restore the microbialbalance on the surface of the skin. The CTFA International CosmeticIngredient Dictionary and Handbook, Eleventh Edition 2005, and the 2004CTFA International Buyer's Guide, both of which are incorporated byreference herein in their entirety, describe a wide variety ofnon-limiting cosmetic and pharmaceutical ingredients commonly used inthe skin care industry, that are suitable for use in the compositions ofthe exemplary embodiments described herein. Examples of these functionalclasses include: abrasives, anti-acne agents, anticaking agents,antioxidants, binders, biological additives, bulking agents, chelatingagents, chemical additives; colorants, cosmetic astringents, cosmeticbiocides, denaturants, drug astringents, emulsifiers, externalanalgesics, film formers, fragrance components, opacifying agents,plasticizers, preservatives (sometimes referred to as antimicrobials),propellants, reducing agents, skin bleaching agents, skin-conditioningagents (emollient, miscellaneous, and occlusive), skin protectants,solvents, surfactants, foam boosters, hydrotropes, solubilizing agents,suspending agents (nonsurfactant), sunscreen agents, ultraviolet lightabsorbers, detackifiers, and viscosity increasing agents (aqueous andnonaqueous). Examples of other functional classes of materials usefulherein that are well known to one of ordinary skill in the art includesolubilizing agents, sequestrants, keratolytics, topical activeingredients, and the like.

The sanitizing compositions exhibit a pH in the range of from about 2.5to about 12.0, or a pH in the range of from about 3.5 to about 8, or inthe range of from about 4.0 and about 7.5. When necessary, a pHadjusting agent or constituent may be used to provide and/or maintainthe pH of a composition. Exemplary pH adjusting agents include, but arenot limited to, organic acids, such as citric acid, lactic acid, formicacid, acetic acid, proponic acid, butyric acid, caproic acid, oxalicacid, maleic acid, benzoic acid, carbonic acid, and the like.

The form of the composition of the exemplary embodiments describedherein is not particularly limited. In one or more embodiments,sanitizing compositions of the exemplary embodiments described hereinmay be formulated as a foamable composition, a thickened gelcomposition, a sprayable liquid, a rinse, or may be applied to a wipe.

In one or more embodiments, the sanitizing composition of the exemplaryembodiments described herein may be in the form of a thickened gel, withthe inclusion of one or more thickeners and optionally one or morestabilizers. Examples of thickeners and stabilizers include hydroxyethylcellulose hydroxypropyl cellulose, methyl cellulose, carboxymethylcellulose, and ammonium acryloyldimethyltaurate/VP copolymer. Where thethickener or stabilizer is starch-based, the thickener or stabilizer maybe present in an amount of up to about 10.0 wt. %, or in an amount offrom about 0.1 to about 5.0 wt. %, or from about 0.2 to about 1.0 wt. %,based on the total weight of the sanitizing composition. Where thethickener or stabilizer is a synthetic polymer, the thickener orstabilizer may be present in an amount of up to about 15.0 wt. %, orfrom about 0.05 to about 5.0 wt. %, or from about 0.1 to about 1.0 wt.%, based on the total weight of the sanitizing composition.

In one or more exemplary embodiments, the sanitizing composition may bethickened with polyacrylate thickeners such as those conventionallyavailable and/or known in the art. Examples of polyacrylate thickenersinclude carbomers, acrylates/C₁₀₋₃₀ alkyl acrylate crosspolymers,copolymers of acrylic acid and alkyl (C₅-C₁₀) acrylate, copolymers ofacrylic acid and maleic anhydride, and mixtures thereof. In one or moreembodiments, the gel composition includes an effective amount of apolymeric thickener to adjust the viscosity of the gel to a viscosityrange of from about 1000 to about 65,000 centipoise (cP). In oneembodiment, the viscosity of the gel is from about 5000 to about 35,000cP, and in another embodiment, the viscosity is from about 10,000 toabout 25,000 cP. The viscosity is measured by a Brookfield RV Viscometerusing RV and/or LV Spindles at 22° C.+/−3° C.

As will be appreciated by one of skill in the art, the effective amountof thickener will vary depending on a number of factors, including theamount of alcohol and other ingredients in the gel composition. In oneor more embodiments, an effective amount of thickener is at least about0.01 wt. %, based on the total weight of the gel composition. In otherembodiments, the effective amount is at least about 0.02 wt. %, or atleast about 0.05 wt. %, or at least about 0.1 wt. %. In some exemplaryembodiment, the effective amount of thickener is at least about 0.5 wt.%, or at least about 0.75 wt. %, based on the total weight of the gelcomposition. In one or more embodiments, the compositions according tothe exemplary embodiments described herein comprise up to about 10.0 wt.% of a polymeric thickener, based on the total weight of the gelcomposition. In certain embodiments, the amount of thickener is fromabout 0.01 to about 1.0 wt. %, or from about 0.02 to about 0.4 wt. %, orfrom about 0.05 to about 0.3 wt. %, based on the total weight of the gelcomposition. The amount of thickener may be from about 0.1 to about 10.0wt. %, or from about 0.5% to about 5.0 wt. %, or from about 0.75 toabout 2.0 wt. %, based on the total weight of the gel composition.

In one or more embodiments, the gel composition may further comprise aneutralizing agent. Examples of neutralizing agents include amines,alkanolamines, alkanolamides, inorganic bases, amino acids, includingsalts, esters and acyl derivatives thereof. Exemplary neutralizingagents include triethanolamine, sodium hydroxide, monoethanolamine anddimethyl stearylamine. Other neutralizing agents are also known, such asHO(C_(m)H_(2m))₂NH, where m has the value of from 2 to 3, andaminomethyl propanol, aminomethyl propanediol, and ethoxylated amines,such as PEG-25 cocamine, polyoxyethylene (5) cocamine (PEG-5 cocamine),polyoxyethylene (25) cocamine (PEG-25 cocamine), polyoxyethylene (5)octadecylamine (PEG-S stearamine), polyoxyethylene (25) octadecylamine(PEG-25 stearamine), polyoxyethylene (5) tallowamine (PEG-5tallowamine), polyoxyethylene (15) oleylamine (PEG-15 oleylamine),polyethylene (5) soyamine (PEG-5 soyamine), and polyoxyethylene (25)soyamine (PEG-15 soyamine). A number of these are commercially availableunder the trade name of Ethomeen® from Akzo Chemie America, ArmakChemicals of Chicago, Ill.

In some exemplary embodiments the neutralizing agent includes at leastone of sodium hydroxide or sodium hydroxide precursors. Solutions ofsodium hydroxide in water are non-limiting examples of neutralizerscontaining sodium hydroxide.

The neutralizing agent is employed in an effective amount to neutralizea portion of the carboxyl groups of the thickening agent, and producethe desired pH range. The pH of un-neutralized thickening agentdispersed in water is generally acidic. For example, the pH of Carbopol®polymer dispersions is approximately in the range of 2.5 to 3.5,depending upon the polymer concentration. An effective amount ofneutralizing agent, when added to the thickener dispersion, adjusts thepH to a desired range of about 4.1 to 4.8, or of about 4.2 to 4.6. Theamount of neutralizing agent necessary to effect this pH range will varydepending upon factors such as the type of thickening agent, the amountof thickening agent, etc. However, in general, amounts less than 1.0% byweight and ranging from about 0.001 to about 0.3 wt. %, based on thetotal weight of the sanitizing composition of the neutralizing agent areconsidered sufficient and effective.

In one or more embodiments, the sanitizing composition is formulated asa foamable composition. One or more foam agents may optionally beincluded in the foamable composition.

Any foaming agent conventionally known and used may be employed in thesanitizing composition. In one or more embodiments, the foam agentcomprises a non-ionic foam agent such as decyl glucoside or anamphoteric foam agent such as cocamidopropylbetaine. In one or moreembodiments, the amount of nonionic or amphoteric foam agent is fromabout 0.5 to about 3.5 wt. %, in other embodiments from about 1.0 toabout 3.0 wt. %, based on the total weight of the sanitizingcomposition. In one or more embodiments, the amount of decyl glucosideor cocamidopropylbetaine is from about 0.5 to about 3.5 wt. %, in otherembodiments from about 1.0 to about 3.0 wt. %, based on the total weightof the sanitizing composition.

In some exemplary embodiments, the foaming agents include one or more ofsilicone glycol and fluorosurfactants. Silicone glycols may be generallycharacterized by containing one or more Si—O—Si linkages in the polymerbackbone. Silicone glycols include organopolysiloxane dimethiconepolyols, silicone carbinol fluids, silicone polyethers, alkylmethylsiloxanes, amodimethicones, trisiloxane ethoxylates, dimethiconols,quaternized silicone glycols, polysilicones, silicone crosspolymers, andsilicone waxes.

Examples of silicone glycols include dimethicone PEG-7 undecylenate,PEG-10 dimethicone, PEG-8 dimethicone, PEG-12 dimethicone,perfluorononylethyl carboxydecal PEG 10, PEG-20/PPG-23 dimethicone,PEG-11 methyl ether dimethicone, bis-PEG/PPG-20/20 dimethicone, siliconequats, PEG-9 dimethicone, PPG-12 dimethicone, fluoro PEG-8 dimethicone,PEG-23/PPG-6 dimethicone, PEG-20/PPG-23 dimethicone, PEG 17 dimethicone,PEG-5/PPG-3 methicone, bis-PEG-18 methyl ether dimethyl silane,bis-PEG-20 dimethicone, PEG/PPG-20/15 dimethicone copolyol andsulfosuccinate blends, PEG-8 dimethicone\dimmer acid blends, PEG-8dimethicone\fatty acid blends, PEG-8 dimethicone\cold pressed vegetableoil\polyquaternium blends, random block polymers and mixtures thereof.

The amount of silicone glycol foam agent is not particularly limited, solong as an effective amount to produce foaming is present. In certainembodiments, the effective amount to produce foaming may vary, dependingon the amount of alcohol and other ingredients that are present. In oneor more embodiments, the composition includes at least about 0.002 wt. %of silicone glycol foam agent, based on the total weight of thecomposition. In another embodiment, the composition includes at leastabout 0.01 wt. % of silicone glycol foam agent, based on the totalweight of the sanitizing composition. In yet another embodiment, thecomposition includes at least about 0.05 wt. % of silicone glycol foamagent, based on the total weight of the sanitizing composition.

In some exemplary embodiments, the foam agent is present in an amount offrom about 0.002 to about 4.0 wt. %, or in an amount of from about 0.01to about 2.0 wt. %, based on the total weight of the composition. It isenvisioned that higher amounts may also be effective to produce foam.All such weights as they pertain to listed ingredients are based on theactive level, and therefore, do not include carriers or by-products thatmay be included in commercially available materials, unless otherwisespecified.

In other embodiments, it may be desirable to use higher amounts of foamagent. For example, in certain embodiments where the foaming compositionof the exemplary embodiments described herein includes a cleansing orsanitizing product that is applied to a surface and then rinsed off,higher amounts of foam agent may be employed. In these embodiments, theamount of foam agent is present in amounts up to about 35.0 wt. %, basedon the total weight of the sanitizing composition.

The sanitizing composition of the exemplary embodiments described hereinmay be formulated as an aerosol or non-aerosol foamable composition. Insome exemplary embodiments the sanitizing composition is dispensed froman unpressurized or low-pressure dispenser which mixes the compositionwith air.

In one or more embodiments, the viscosity of the non-aerosol foamablecomposition is less than about 100 mPas, in one embodiment less thanabout 50 mPas, and in another embodiment less than about 25 mPas.

The composition of the exemplary embodiments described herein may beemployed in any type of dispenser typically used for gel products, forexample pump dispensers. A wide variety of pump dispensers are suitable.Pump dispensers may be affixed to bottles or other free-standingcontainers. Pump dispensers may be incorporated into wall-mounteddispensers. Pump dispensers may be activated manually by hand or footpump, or may be automatically activated. Useful dispensers include thoseavailable from GOJO Industries under the designations NXT®, TFX™, DPX™,FMX™, ADX™ LTX™, and CXT™ as well as traditional bag-in-box dispensers.Examples of dispensers are described in U.S. Pat. Nos. 5,265,772,5,944,227, 6,877,642, 7,028,861, 7,611,030, 7,621,426, 8,740,019,8,991,657, 9,027,790, 9,073,685, 9,101,250, and 9,204,767, all of whichare incorporated herein by reference. In one or more embodiments, thedispenser includes an outlet such as a nozzle, through which thecomposition is dispensed. In some exemplary embodiments, the sanitizingcomposition is used in dispensers that employ foaming pumps, whichcombine ambient air or an inert gas and the composition in a mixingchamber and pass the mixture through a mesh screen.

In one or more embodiments, the sanitizing composition is integratedinto wipe composition. Wipe compositions in accordance with theexemplary embodiments described herein include at least one alcohol, aC₁₋₁₀ alkanediol enhancer, and are applied to a wipe substrate. In someexemplary embodiments, the wipe composition is alcohol-free.

Wipe substrates used in antimicrobial wipes are further described inU.S. Pat. Nos. 5,686,088, 6,410,499, 6,436,892, 6,495,508, 6,844,308,9,096,821, which are incorporated herein by reference. In one or moreembodiments, the wipe may comprise a laminate formed byspunbonding/meltblowing/spunbonding (SMS). Generally, an SMS materialcontains a meltblown web sandwiched between two exteriors spunbond webs.SMS materials are further described in U.S. Pat. Nos. 4,041,203,5,169,706, 5,464,688, and 4,766,029, and are commercially available, forexample from Kimberly-Clark Corporation under marks such as Spunguard 7and Evolution 7. The SMS laminate may be treated or untreated.

In other exemplary embodiments, the sanitizing composition is formulatedas a spray. In some exemplary embodiments, the spray is a nasal spraythat is designed to be used in the nose. The particular delivery methodof the nasal spray is not particularly limited. Exemplary deliverymethods and base compositions which are envisioned as suitable for theexemplary embodiments disclosed herein are disclosed in U.S. Pat. Nos.8,053,005; 8,158,163; 8,778,415; 8,999,406; and 9,463,212, all to GlobalLife Technologies Corp., all of which are incorporated herein byreference. In some exemplary embodiments, the nasal spray is used in ahospital to treat some or all admitted patients. In some exemplaryembodiments, hospital and out-patient healthcare employees are treatedwith the nasal spray. In some exemplary embodiments, patients with ahistory or recurrent folliculitis, furunculosis, and/or staph aureus aretreated with the nasal spray. In still other exemplary embodiment,family members of patients suffering from these conditions are treatedwith the nasal spray.

In some exemplary embodiments, the nasal spray sanitizing compositioncomprises one or more C₁₋₈ alcohols and an active ingredient. In someexemplary embodiments, the active ingredient comprises one or more of aprobiotic, a probiotic derivative, and a prebiotic. In some exemplaryembodiments, the active ingredient comprises one or more probiotics. Insome exemplary embodiments, the probiotic is a topical probiotic. Bytopical probiotic it is meant a probiotic that is designed to be used onthe skin or other part of a mammalian body. In some exemplaryembodiments, the nasal spray is essentially free or completely free oforal probiotics. Oral probiotics are those that are meant to beingested. By “essentially free of oral probiotics” it is meant that thenasal spray contains no greater than 5.0 wt. %, preferably no greaterthan 1.0 wt. %, and more preferably no greater than 0.5 wt. % peroxides.In some exemplary embodiments, the nasal spray sanitizing compositioncomprises various fragrances. In some exemplary embodiments, applicationof the nasal spray reduces pathogen binding in the nose by an amountthat is statistically significant, as compared to an otherwise identicalnasal spray without the active ingredient.

In some exemplary embodiments, the nasal spray kills staph bacteria,such as that associated with and responsible for methicillin-resistantStaphylococcus Aureus (MRSA). In some exemplary embodiments, the nasalspray with alcohol and active ingredient helps to reestablish thehealthy normal nasal flora biome. In some exemplary embodiments, thenasal spray provides efficacy against pathogenic bacteria and does notpromote bacterial-resistance developing even with extended use. In someexemplary embodiments, the nasal spray helps to fight and defend againstpathogens associated with of Clostridium Difficile infections of theintestine, C. difficile, MRSA, folliculitis, furunculosis, and staphaureus.

In some exemplary embodiments, the sanitizing composition decreases theproduction and/or activity of pro-inflammatory factors such asinterleukins, including interleukin-8 (IL-8). Over-expression of IL-8 isa biomarker of skin irritation. IL-8 is associated with inflammation andplays a role in colorectal cancer. In some exemplary embodiments, asanitizing composition comprising up to about 15.0 wt. % of the activeingredient in water is able to reduce the relative production and/oractivity of pro-inflammatory factors by at least about 50%, or at leastabout 70%, or at least about 78%, as compared to an otherwise identicalcontrol composition without the active ingredient. In other exemplaryembodiments, a sanitizing composition comprising up to about 15.0 wt. %of an active ingredient in ethanol is able to reduce the relativeproduction and/or activity of pro-inflammatory factors by at least about15%, or at least about 25%, or at least about 30%, as compared to anotherwise identical control composition without the active ingredient.

In some exemplary embodiments, the sanitizing composition increases theexpression of Involucrin. Involucrin is a protein component of humanskin and is encoded in humans by the IVL gene. In some exemplaryembodiments, a sanitizing composition comprising up to about 15.0 wt. %of an active ingredient is able to increase the relative Involucrinproduction and/or activity by at least 50%, or at least 70%, or at least90% or at least 100%, as compared to an otherwise identical controlcomposition not including the active ingredient.

In some exemplary embodiments, the sanitizing composition increases theproduction and/or activity of cadherins. In some exemplary embodiments,the increased cadherins are desmosomals, such as DCS3. In some exemplaryembodiments, a sanitizing composition comprising up to about 15.0 wt. %of an active ingredient is able to increase the relative productionand/or activity cadherins, such as DCS3 by at least about 25%, or atleast 35%, or at least 50%, or at least 57%, as compared to an otherwiseidentical control composition not including the active ingredient.

In some exemplary embodiments, a sanitizing composition comprising up toabout 15.0 wt. % of an active ingredient increases the production and/oractivity of defensins, such as HBD-2. HBD-2 is a low molecular weightAMP produced by epithelia cells and is encoded by the DEFB4 gene. Itexhibits potent antimicrobial activity against Gram-negative bacteriaand Candida. In some exemplary embodiments, a sanitizing compositioncomprising up to about 15.0 wt. % of an active ingredient in water isable to increase the relative production and/or activity of defensins,such as HBD-2 by at least about 25%, or at least about 35%, or at leastabout 45%, or at least about 55%, or at least about 65%, or at leastabout 75%, or at least about 90%, or at least about 100%, or at leastabout 125%, or at least 140%, as compared to an otherwise identicalcontrol composition without the active ingredient.

EXAMPLES

The following examples are included for purposes of illustration and arenot intended to limit the scope of the methods described herein.

Example 1

Sanitizing compositions with Bonicel™ were tested for their ability todecrease production and/or activity of Interleukin 8 (IL-8 or CXCL8),which is a chemokine and proinflammatory cytokine produced bymacrophages and other cell types such as epithelial cells. IL-8 issecreted from keratinocytes in skin in response to inflammatory stimuli.

For Control A, human dermal keratinocytes were left untreated. Noirritation is expected, and therefore Control A provides a baseline (setas 0). For Control B, IL-8 is induced in human dermal keratinocytes byapplying a surfactant mixture that is a combination of sodium laurethsulfate and polyquaternium-10 (set as 100%). Samples of Bonicel™ in botha water composition and ethanol composition were tested for theirability to alter IL-8 expression. For all other samples, the humandermal keratinocytes are co-treated with the surfactant mixture and acomposition containing indicated concentration of Bonicel™. DecreasedIL-8 expression reflects an ingredient's anti-irritation activity. Inorder to carry out the test method, an assay kit was employed that wasobtained from R&D Systems: Human CXCL8/IL-8 Duoset ELISA Kit (DY208).ELISA was performed after overnight treatment using by applying 100μl/well of culture medium according to the manufactory instruction ofthe ELISA kit. The results were measured using a colorimeter, absorbancewas measured at 450 nanometers (nm) within 30 minutes. Wavelengthcorrection was set to 570 nm.

The results showed a sanitizing composition with Bonicel™ was able toreduce the relative IL-8 production and/or activity. A relative decreasein IL-8 production and/or activity of about 78% was observed for asanitizing composition with 1.0% Bonicel™, water, and a surfactant, ascompared to a control composition with water and a surfactant. Arelative decrease in IL-8 production and/or activity of 30% was observedfor a sanitizing composition with 1.0% Bonicel™, ethanol, and asurfactant, as compared to a control composition with ethanol and asurfactant. The results are depicted graphically in FIG. 1 .

Example 2

An in vitro study was conducted to study a sample of Bonicel™specifically for its ability to increase production and/or activity ofInvolucrin.

Neonatal Human Epidermal Keratinocytes (NHEK; Life Technology, GrandIsland, N.Y., USA) were cultured with keratinocyte growth medium (KGM,Medium 154: M-154-500 Life Technology with supplements S-001, LifeTechnologies). Keratinocytes were treated with the sample compositionsin a 6-well plate overnight. After washing with cold phosphate-bufferedsaline (PBS), total RNAs were prepared from each well. Real-TimeQuantitative Reverse Transcription PCR (qRT-PCR) was performed to detectthe target genes (Involucrin) expression level using a One-step TaqMan®RT-PCR kit (Life Technologies).

The results showed that Bonicel™ increased the relative productionand/or activity of Involucrin. A relative increase in Involucrinproduction and/or activity of about 103% was observed for 0.1% Bonicel™as compared to the KGM medium control culture. This increase shows thatBonicel™ can stimulate Involucrin production and/or activity inkeratinocyte to promote skin keratinocyte differentiations and improveskin barrier function. The results are depicted graphically in FIG. 2 .

Example 3

An in vitro study was conducted to study a sample of Bonicel™specifically for its ability to increase production and/or activity ofdesmocollin-3 (DSC3).

Neonatal Human Epidermal Keratinocytes (NHEK; Life Technology, GrandIsland, N.Y., USA) were cultured with keratinocyte growth medium (KGM,Medium 154: M-154-500 Life Technology with supplements S-001, LifeTechnologies). Keratinocytes were treated with the sample compositionsin a 6-well plate overnight. After washing with cold phosphate-bufferedsaline (PBS), total RNAs were prepared from each well. Real-TimeQuantitative Reverse Transcription PCR (qRT-PCR) was performed to detectthe target genes (DSC3) expression level using a One-step TaqMan® RT-PCRkit (Life Technologies).

The results showed that Bonicel™ increased the relative productionand/or activity of DSC3. A relative increase in DCS3 production and/oractivity of about 57% was observed for 0.1% Bonicel™ as compared to theKGM medium culture. This increase shows that Bonicel™ can stimulate theskin junction biomarker DSC3 production and/or activity in keratinocytesto improve skin barrier function. The results are depicted graphicallyin FIG. 3 .

Example 4

In vitro studies were also run with Bonicel™ specifically to determineits ability to simulate production and/or activity of humanbeta-defensin 2 (HBD-2). Bonicel™ was tested at concentrations of both0.1% and 1.0% and in each of dermatological carriers, ethanol and water.

Neonatal Human Epidermal Keratinocytes (NHEK; Life Technology, GrandIsland, N.Y., USA) were cultured with keratinocyte growth medium (KGM,Medium 154: M-154-500 Life Technology with supplements S-001, LifeTechnologies). NHEK were seeded into 96-well plates at a density of10000 cells in 200 μl medium per well. After 48 hours, the cells wereincubated with varying concentrations of each ingredient solution in aculture medium (KGM) overnight (16 hours) at 37° C., 5% CO₂ and 95%humidity at four replicates for each concentration. Each of these activeingredients was tested at the different concentration of weight percentsbased on the weight of the total culture. Each of these compositions wascompared to a control culture medium.

HBD-2 was detected using HBD-2 ELISA developing kits (commerciallyavailable from Peprotech). ELISA were performed according to themanufactory instructions of each kit by adding 100 μl/well of culturemedium after overnight treatment. The substrate of ELISA reaction wasusing the substrate reagent from R&D Systems (DY999), and the reactionswere stopped by adding 50 μl of IN H₂SO₄ in each well. The results weremeasured using a colorimeter, absorbance was measured at 450 nanometers(nm) within 30 minutes. Wavelength correction was set to 570 nm. Theconcentration of each sample was calculated using ELISA standard curve.

The results showed the Bonicel™ is able to increase the productionand/or activity of HBD-2 both in a composition with water and in acomposition that had been in contact with ethanol. Relative increases inHBD-2 production and/or activity of about 44% and about 90% wereobserved for 0.1% Bonicel™ in a composition with water and 1.0% Bonicel™in a composition with water, respectively. Additionally relativeincreases in HBD-2 production and/or activity of about 125% and about144% were observed for 0.1% Bonicel™ in a composition that had been incontact with ethanol and 1.0% Bonicel™ in a composition that had been incontact with ethanol, respectively. From these results, it is alsoapparent that Bonicel™ does not lose its ability to increase theproduction and/or activity of HBD-2 and in fact, the effectiveness ofthe composition actually increased substantially when combined with theethanol. The results for Bonicel™ in a water composition are depicted inFIG. 4 and the results for Bonicel™ that had been in contact withethanol composition are depicted in FIG. 5 .

Example 5

The effect of exemplary sanitizing compositions was investigated forpathogen blocking potential. Methicillin resistant Staphylococcus aureusstrain Mu50 ATCC 33591, Escherichia coli strain K12 was tested againstthe following exemplary topical compounds: DMEM (cell culture medium,control), 100 nM dexamethasone (DEX, control steroidalanti-inflammatory), 0-5% Ecoskin (α-gluco-oligosaccharide,fructo-oligosaccharide and inactivated Lactobacillus), 0-5% Bacillusferment, and 0-5% of a prebiotic blend of inulin andfructo-oligosaccharide.

Differentiated colonic epithelial cells were treated with the topicalcompounds and a bacterial strain was then added individually. Themicrobe was grown to the mid-log phase in an acceptable medium and theconcentration adjusted so that the amount of bacteria added to the wellswas approximately 100 microbes per well (in a 96 well tray with totalvolume of 100 uL). The cells were then incubated with each bacterialstrain for one hour. A Gentamicin protection assay was used to determineadhered and invaded bacteria. Polymerase chain reaction (PCR) using 16Sgene primers was used to determine the number of adhered bacteria, aswell as the number of bacteria that invaded into the host cells.

FIG. 6 illustrates the dose-dependent response of Staphylococcus aureusadhesion and invasion potential. Bacillus ferment had a consistentincrease in the dose response. Particularly, 5% Bacillus fermentresulted in the lowest adhesion occurrence overall.

Example 6

The effect of exemplary sanitizing compositions was investigated for itsability to kill more transient bacteria than resident. Each test groupcontained 6 participants for the extended use impacts experiment. Eachday, prior to testing, both hands were washed with a bland soap toremove the transient bacteria that existed on the participant's handsbefore they entered the laboratory. In the immediate impact experiment,hands were intentionally contaminated by adding a mixture of Serratiamarsescens and Enterococcus faecalis to the palmar side of the hands andrubbing for 30 seconds. Hand bacteria were sampled using a glove juicemethod followed by plated onto CHROMAgar™ orientation plates with andwithout antibiotics. One hand was sampled before application of eachtest article and then the other hand was sampled to obtain thepost-hygiene use measurement. CFU counts before and after were comparedto obtain LogioCFU reduction values. In the extended use experiment,both hands were sampled using the glove juice method before and thenagain after 12 days of use of either a hand sanitizer or a topicalantibiotic cream five times a day, or after avoiding all exposure toantimicrobials. Plate counts of viable bacteria were obtained and thecomposition of the hand bacteria was determined via 16S rRNA genesequencing of DNA extracted from the glove juice solutions before andafter the 12 days of the trial.

As illustrated in FIG. 7 , the results indicated that a 1.0% Bonicel™composition killed significantly more transient bacteria than residentbacteria, thereby restoring the skin's natural balance.

Although embodiments of the invention have been described herein, itshould be appreciated that many modifications can be made withoutdeparting from the spirit and scope of the general inventive concepts.All such modifications are intended to be included within the scope ofthe invention, which is to be limited only by the following claims.

What is claimed is:
 1. A sanitizing composition for restoring skin'snatural balance of bacteria, the composition comprising: from about0.005 wt. % to about 15.0 wt. % of an active ingredient selected fromthe group consisting of one or more strains of Lactobacillus,Clostridia, Saccharomyces, Lactococcus, Pedicoccus, Enterococcus,Escherichia, Alcaligenes, Corynebacterium, Bacillus, Propionibacterium,and combinations thereof; at least one polymeric thickener; at leastabout 50 wt. % of one or more ingredients with a sanitizing effect, theone or more ingredients with a sanitizing effect comprising alcohol, aquaternary ammonium compound, or a combination thereof; and up to about30 wt. % water, wherein the sanitizing composition reduces pathogenbinding on skin by a statistically significant amount, as compared to anotherwise identical sanitizing composition without the activeingredient.
 2. The sanitizing composition of claim 1, wherein the one ormore ingredients with a sanitizing effect is present in an amount aboveabout 70 wt. %, based on the total weight of the sanitizing composition.3. The sanitizing composition of claim 1, wherein the sanitizingcomposition comprises from about 0.05 wt. % to about 5.0 wt. % of theactive ingredient, based on the total weight of the sanitizingcomposition.
 4. The sanitizing composition of claim 1, wherein thesanitizing composition further comprises one or more skin conditioningagents.
 5. The sanitizing composition of claim 4, wherein the one ormore skin conditioning agents comprises one or more humectants, selectedfrom the group consisting of propylene glycol, hexylene glycol,1,4-dihydroxyhexane, 1,2,6-hexanetriol, sorbitol, butylene glycol,caprylyl glycol, propanediols, methyl propane diol, dipropylene glycol,triethylene glycol, glycerin (glycerol), polyethylene glycols,ethoxydiglycol, polyethylene sorbitol, glyceryl caprylate/caprate, andcombinations thereof.
 6. The sanitizing composition of claim 1, whereinthe sanitizing composition further comprises one or more plug preventingadditives in an amount up to about 20.0 wt. %, based on the total weightof the sanitizing composition.
 7. The sanitizing composition of claim 1,wherein the sanitizing composition further comprises one or moremoisturizing esters, selected from the group consisting of cetylmyristate, cetyl myristoleate, cetyl esters, diisopropyl sebacate,isopropyl myristate, and combinations thereof.
 8. The sanitizingcomposition of claim 7, wherein the moisturizing ester is present in anamount up to about 10.0 wt. %, based on the total weight of thesanitizing composition.